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CREDIT AUTHOR’S STATEMENT
All listed authors have contributed to this study and reviewed the finished manuscript.
- Study concepts: C Touboul, V Lavoue, S Bendifallah, F Rodriguez, M Ballester, P Collinet, L Ouldamer, O Graesslin, C Huchon, F Golfier and X Carcopino
- Study design: T Moussilmani, X Carcopino, F Rodriguez and S Knight - Data acquisition : PA Bolze, Y Kerbage, G Atrous, L Dion, Y Dabi, E Raimond, M Mimouni and
A Benbara - Quality control of data and algorithms: X Carcopino, F Rodriguez and J Mancini - Data analysis and interpretation: X Carcopino, T Moussilmani, S Knight and J Mancini - Statistical analysis: J Mancini, T Moussilmani and X Carcopino - Manuscript preparation: X Carcopino, T Moussilmani and J Mancini - Manuscript editing: X Carcopino, T Moussilmani, S Knight, Y Dabi, F Rodriguez and J Mancini - Manuscript review: All authors
Pr Xavier CARCOPINO MD, PhD Corresponding author
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PROGNOSIS IMPACT OF POSTTREATMENT PELVIC MRI IN PAT IENTS
TREATED FOR STAGE IB2-IIB CERVICAL CANCER WITH CHEM ORADIATION
THERAPY
Authors: Tiphaine Moussilmani1, Sophie Knight1, Julien Mancini2, Cyril Touboul3, Florence
Rodriguez4, Pierre Adrien Bolze5, Sofiane Bendifallah3, Marcos Ballester6, Pierre Collinet7,
Yohan Kerbage7, Lobna Ouldamer8, Geoffroy Atrous8, Vincent Lavoué9, Ludivine Dion9,
Yohann Dabi10, Emilie Raimond11, Olivier Graesslin11, Cyrille Huchon12, Myriam Mimouni12,
Alexandre Bricou13, François Golfier5, Xavier Carcopino1*.
Affiliations:
1. Department of Obstetrics and Gynaecology, Hôpital Nord, APHM, Aix-Marseille
University (AMU), Univ Avignon, CNRS, IRD, IMBE UMR 7263, 13397, Marseille,
France
2. Aix Marseille Univ, APHM, Inserm, IRD, SESSTIM, Hop Timone, BioSTIC,
Marseille, 13385 France
3. Department of Gynaecology and Obstetrics, Tenon University Hospital, Assistance
Publique des Hôpitaux de Paris (AP-HP), Faculté de Médecine Sorbonne Université,
Institut Universitaire de Cancérologie (IUC), France.
4. Department of Radiology, Hôpital Nord, APHM, Marseille, France
5. Department of Gynaecologic and Oncologic Surgery and Obstetrics, Centre
Hospitalier Universitaire Lyon Sud, Hospices Civils de Lyon, Université Lyon 1,
France
6. Department of Gynaecologic and Breast Surgery, Groupe Hospitalier Diaconesses
Croix Saint Simon, 125 rue d’Avron, 75020, Paris
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7. Department of Gynaecologic surgery, Hôpital Jeanne de Flandre, CHRU LILLE, Rue
Eugene avinée 59037 lille cedex, France
8. Department of Gynaecology. CHRU de Tours. Hôpital Bretonneau. INSERM unit
1069, 2 boulevard Tonnelé. 37044 TOURS. France.
9. Department of Gynaecology, CHU de Rennes, France. INSERM 1242, COSS,
Rennes. Université de Rennes 1. France.
10. Departement of Obstetrics and Gynaecology, Centre Hospitalier Intercommunal,
Créteil, France. Université de Médecine Paris Est Créteil.
11. Department of Obstetrics and Gynaecology, Alix de Champagne Institute, Centre
Hospitalier Universitaire, 45 rue Cognacq-Jay, 51092 Reims, FRANCE
12. Department of gynaecology, CHI Poissy-St-Germain, Université Versailles-Saint-
Quentin en Yvelines, EA 7285 Risques cliniques et sécurité en santé des femmes,
Université Versailles-Saint-Quentin en Yvelines, Versailles, France
13. Department of Obstetrics and Gynaecology, Jean-Verdier University Hospital,
Assistance Publique des Hôpitaux de Paris, University Paris 13, France
* Corresponding author: Xavier Carcopino, MD, PhD
Department of Obstetrics and Gynaecology
Assistance Publique des Hôpitaux de Marseille (APHM)
Hôpital Nord, Chemin des Bourrely, 13015 Marseille, France
Phone: 0033 4 91 96 46 72
Email: [email protected]
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ABSTRACT
Objectives: To evaluate the performances of systematic posttreatment pelvic magnetic
resonance imaging (PPMRI) in predicting prognosis of patients treated with chemoradiation
therapy (CRT) for locally advanced cervical cancer (LACC).
Materials and methods: Multi-institutional data from 216 patients presenting FIGO IB2-IIB
cervical cancer for which PPMRI was performed following CRT were retrospectively
reviewed. Incomplete response was defined as the identification of persistent lesion on
PPMRI. Primary endpoints were patients’ 5-year recurrence free (RFS) and overall (OS)
survivals. Secondary endpoint was the identification of residual histologic disease on
hysterectomy specimens when completion surgery was performed.
Results: PPMRI identified an incomplete response in 102 (47.2%) cases. A 70% or more
reduction in tumor size on PPMRI was identified as the best predictive cut-off for recurrence
(37.7% sensitivity and 78.7% specificity) and death (50% sensitivity and 77.9% specificity)
with significant impact on those risks (HRa: 0.42; 95%CI: 0.23-0.77 and HRa: 0.18; 95%CI:
0.06-0.50, respectively). Completion hysterectomy was performed in 117 (54.4%) cases, with
histologic residual disease in 55 (47.4%). PPMRI demonstrated 74.5% sensitivity and 50.8%
specificity in predicting residual disease. Although survival of patients with complete
response at PPMRI was not impacted by completion hysterectomy, it significantly increased
5-year RFS and OS of those with incomplete response: 38.7% vs. 65.3% (p<0.001) and 63%
vs. 82.9% (p=0.038), respectively.
Conclusion: A 70% or more reduction of in tumor size on PPMRI following CRT in patients
with LACC is predictive of RFS and OS. PPMRI could help triaging patients who could
benefit from completion hysterectomy.
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248 words
Keywords: Pelvic MRI; cervical cancer; prognosis; survival; recurrence; chemoradiation
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INTRODUCTION
With 569 847 new cases and 311 365 deaths reported in 2018, cervical cancer represents a
genuine worldwide health challenge and the fourth cancer among women [1]. It remains a
dramatic disease since it affects young women with high mortality. Although surgery is
commonly performed for the management of microinvasive cervical cancer and early FIGO
stages, combined chemoradiation therapy (CRT) has been demonstrated as the treatment of
choice for patients diagnosed with locally advanced disease [2]. Such combined therapy is
now considered as a standard as it was proven to improve overall and progression-free
survival and to reduce local and distant recurrences [3–5]. However, despite obvious efficacy
of CRT, recurrences are unfortunately still common, occurring mostly within the first two
years of follow-up [6,7]. Additionally to the FIGO staging, pelvic and para aortic nodal status
and tumor dimensions have been identified as major initial prognosis factors [7,8]. Another
key prognosis factor is the identification of posttreatment cervical residual disease. However,
the proper evaluation of patients’ response to CRT remains challenging as solely the
histologic analysis of surgical specimen from patients undergoing completion hysterectomy
can reliably asses this parameter.
Pelvic magnetic resonance imaging (MRI) has been shown to be the best imaging
examination for the initial staging of patients diagnosed with cervical cancer [9,10]. It
provides precise characterization of the disease with the ability to determine the exact tumor
dimensions and its local spread with possible involvement of nearby organs such as parameter
and ureters, vagina, bladder and rectum [11,12]. Pelvic MRI is also commonly performed for
the evaluation of tumor’s response following CRT. However, its performances in this precise
indication remains questionable. Although previous studies have shown its ability to predict
patients’ outcome and survival, there is a lack of evidence regarding the ability of
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posttreatment pelvic magnetic resonance imaging (PPMRI) to predict histological cervical
residual disease. Thus, only few studies have correlated PPMRI results with the histological
analysis of hysterectomy specimens in patients who had undergone completion surgery [13–
17]. Additionally, these retrospective studies suffer from limited power with little number of
patients included, ranging from 41 to 159 only [13–17].
The possibility to identify post-RCT residual disease represents a genuine challenge as it
could allow for tailored surgery in selected patients. To date, the benefit of completion
surgery following CRT in locally advanced cervical cancer remains widely debated as it has
not shown any improvement in patients’ survival and is associated with genuine morbidity
[18,19]. Previous data however suggest that completion surgery could improve local control
in patients with partial pathological response [20–23]. Finally, completion surgery allows for
the identification of patients with incomplete histologic response and higher risk of recurrence
that should be submitted to adjuvant therapies [24,25].
The aim of this study was to evaluate the performances of systematic PPMRI in predicting
prognosis of patients treated with CRT for locally advanced cervical cancer. We also
evaluated the ability of PPMRI in predicting cervical histologic residual disease.
METHODS
Study population
Data from all patients treated for stage IB2 to IIB cervical cancer by chemoradiation therapy
(CRT) in 9 French institutions from April 1996 to May 2016, and for which a systematic
PPMRI was performed were retrospectively analyzed. Patients’ initial characteristics,
therapeutic management and follow up were retrieved from medical charts. Primary endpoint
was patients’ survival. Secondary endpoint was the histologic identification of residual
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disease on hysterectomy specimens when completion surgery was performed. Informed
consent was obtained from all participants. The study protocol received ethical approval from
the Institutional Review Board of the Collège National des Gynécologues et Obstétriciens
Français (CEROG 2016-GYN-0502).
Patients’ pretreatment evaluation included physical examination, cervical biopsy and/or
diagnostic conization completed with PET/CT and pelvic MRI. The FIGO staging was
established based on the results of physical examination combined with pelvic MRI according
to the 2009 FIGO classification [26]. The retrospective nature of the study did not allow for
the use of the revised 2019 FIGO classification for cervical cancer [9]. The tumor maximal
size was determined on pre-therapeutic pelvic MRI and corresponded to the largest dimension
of the tumor. When indicated, initial surgical nodal staging including pelvic and/or para-aortic
laparoscopic lymphadenectomy was performed. The patients’ lymph node status was
therefore classified according to three categories depending of the findings of PET/CT and/or
surgical nodal staging when performed. Patients were considered as node positive (N+) when
nodal involvement was identified on the pre-therapeutic PET/CT and/or by the surgical nodal
staging. Patients were considered as node negative (N-) only after negative surgical nodal
staging regardless of the results of the imaging. Finally, patients with negative pre-therapeutic
PET/CT but who had not undergone surgical nodal staging or who had had neither pre-
treatment PET/CT nor surgical nodal staging were considered as unknown (Nx).
Treatment modalities were established by a local multidisciplinary committee according to
the French national guidelines. Although all patients did receive CRT, they could either have
received additional vaginal brachytherapy (VBT) and/or completion hysterectomy. Thus, the
following four treatment strategies were recorded: exclusive CRT; CRT followed by VBT;
CRT followed by completion surgery; CRT followed by VBT and completion surgery. The
decision whether to perform completion surgery (i.e. hysterectomy) solely depended on the
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practice of each participating institution, as some systematically did perform completion
hysterectomy whilst others did not, and some considered completion surgery only in cases
with documented residual disease following CRT.
PPMRI was performed within a 3 month delay following the completion of CRT or after
additional VBT when performed. An incomplete response at PPMRI was defined as the
identification of persistent cervical and/or nodal lesion. Cervical and nodal incomplete
response were defined as a persistent cervical lesion and persistent nodal lesion, respectively.
Systematic follow-up included visits every 3 months during the first 2 years, every 6 months
during the 3 following years and annually after 5 years. Follow-up included physical
examination while imaging including PET/CT and/or pelvic MRI was performed in case of
suspected recurrence.
Statistical analysis:
5-year recurrence-free (RFS) and overall (OS) survivals were estimated. RFS and OS were
defined as the duration from the date of primary treatment to recurrence and death,
respectively. In case no event was reported, they were censored at the date of last follow-up.
RFS and OS were estimated for the following variables: age, BMI, parity, menopausal status,
FIGO stage, histology, tumor size, nodal status, treatment modality and results of PPMRI.
Identification of optimal cut-off in the reduction of cervical tumour’s dimension as predictive
factor for RFS and OS was performed using the receiver operator characteristics (ROC) curve
analysis. Multivariate analysis was conducted including variables that were identified as
significant RFS and OS prognostic factors in our study and in literature.
Results of PPMRI were compared to the presence or absence of histologic residual disease on
hysterectomy specimens when completion surgery had been performed. PPMRI diagnostic
performances for histologic residual disease were evaluated using sensitivity and specificity.
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Patient characteristics were reported using counts (%) for categorical variables and mean ±
standard deviation for continuous variables. Chi2 statistics were used to compare indicators of
diagnostic performances. Kaplan-Meier estimates were used to estimate the event-time
distributions, and log-rank test was used to compare the differences among the different
groups in terms of RFS and OS. Hazard Ratios (HR) in univariate analysis and adjusted
Hazard ratios (HRa) in multivariate analysis were estimated using Cox model. A p value of
<0.05 was considered statistically significant. Statistical analysis was performed using IBM
SPSS Statistics version 20.0 (IBM Inc., New York, NY, USA).
RESULTS
Patients
A total of 216 patients with stage IB2 to IIB cervical cancer who received CRT and for which
a systematic posttreatment pelvic MRI had been performed were included in the study.
Patients’ characteristics are reported in Table 1. An incomplete response was identified on
PPMRI in 102 (47.2%) cases. Completion surgery was performed in 117 (54.4%) cases, with
histologic residual disease identified in 55 (47.4%) cases, mean size of histologic residual
disease was 6 mm (±11.0). Median duration of follow-up was 39.2 months (95%CI: 32.4-46).
The 5-year RFS and OS were respectively 60% (95%CI: 53-69) and 82% (95%CI: 75-90).
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Age, mean (± SD) (years) 52.3 (± 12.8) BMI, mean (± SD) (kg/ m²) 25.6 (± 6.0) Parity, mean (± SD) 2.7 (± 2.3) Menopaused 101 (47) FIGO stage IB2 IIA IIB
36 (16.7) 27 (12.5) 153 (70.8)
Histology Squamous Other histology ‡
182 (84.3) 34(15.7)
Tumor size (MRI) (mm) Mean (± SD) ≥ 40
46.8 (± 14.2) 147 (73.1)
Nodal status*£ N- N+ Nx
106 (49.1) 50 (23.1) 60 (27.8)
Treatment modality Exclusive CT/RT CRT + VBT CRT + Completion hysterectomy CRT + VBT + Completion hysterectomy
16 (7.4) 80 (37) 18 (8.3)
102 (47.2) PPMRI Incomplete cervical response Incomplete nodal response Incomplete cervical and/or nodal response
99 (45.8)
11 (6) 102 (47.2)
Completion hysterectomy Cervical residual disease Residual tumor size (± SD) (mm)
117 (54.4) 55 (47.4)
6.0 (± 11.1)
Table 1. Patients’ characteristics (n=216) Values are expressed as n (%), unless otherwise indicated ‡ Adenocarcinomas (n=27) and other histology type (n=7) *Defied as follows: N+ (N+ on PET/CT or N- on PET/CT but N+ after surgical nodal staging or N+ after surgical nodal staging) N- (negative surgical nodal staging) Nx (no PET/CT and no surgical nodal staging or negative PET/CT with no surgical nodal staging) £ Nodal surgical pretherapeutic staging was performed in 145 (67.1%) patients SD: Standard deviation; BMI: Body Mass Index; CRT: chemoradiation therapy; PPMRI: posttreatment pelvic MRI; VBT: vaginal brachytherapy
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Predictive factors for recurrence
The 5-year RFS for patients with an incomplete response at PPMRI was 58.4% vs 61.9% for
patients with complete metabolic response (p=0.55) (Figure 1A). Although the identification
of incomplete response on PPMRI was not found to significantly impact the RFS, the
identification of histologic cervical residual disease in women who had undergone completion
hysterectomy was significantly associated with an increased risk of recurrence (HR: 3.40;
95% CI: 1.6-7.4; p=0.002). Other factor identified to significantly impact the risk of
recurrence was nodal status, with an increased risk of recurrence of Nx and N+ patients when
compared to N- (HRa: 2.25; 95%CI: 1.19-4.28; p=0.01 and HRa: 2.340; 95%CI: 1.21-4.76;
p=0.01, respectively). Compared to patients who were solely treated with CRT, only patients
who received additional VBT followed by completion hysterectomy demonstrated a reduction
in the risk of recurrence (HRa: 0.33; 95%CI: 0.14-0.81; p=0.02) (Table 2). Considering the
reduction in tumor’s size observed when comparing pre and PPMRI, best prediction in
patients’ RFS was found for a threshold of 70% reduction or more (37.7% sensitivity and
78.7% specificity). Thus, compared to others, a reduction ≥70% in tumor’s size was found to
significantly reduce the risk of recurrence (HRa: 0.42; 95%CI: 0.23-0.77; p=0.005) (Table 2)
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HR (95 % CI) p HRa (95 % CI) p
Age (for each extra year) 1.00 (0.98-1.20) 0.89 - - BMI (for 1 kg/m² extra) 0.98 (0.94-1.20) 0.35 - - Parity (for 1 extra birth) 1.06 (0.96-1.16) 0.26 - - Menopaused 0.80 (0.50-1.30) 0.45 - - FIGO stage*
IB2 IIA IIB
1 (ref.)
1.40 (0.50-4.00) 2.30 (1.00-5.00)
0.08 -
0.52 0.04
1 (ref.)
1.57 (0.45-5.53) 2.49 (0.98-6.34)
0.12 -
0.48 0.06
Squamous carcinoma ** 1.00 (0.50-2.00) 0.93 1.03 (0.50-2.12) 0.95 Tumor size (for each extra mm) 1.02 (1.00-1.04) 0.01 1.02 (1.00-1.04) 0.09 Nodal status †
N- Nx N+
1 (ref.)
2.20 (1.20-3.90) 2.90 (1.60-5.20)
<0.001 -
0.01 <0.001
1 (ref.)
2.40 (1.21-4.76) 2.25 (1.19-4.28)
0.02 -
0.01 0.01
Treatment modality ‡ CRT CRT + VBT CRT + Completion hysterectomy CRT + VBT + Completion hysterectomy
1 (ref)
0.60 (0.20-1.30) 0.60 (0.20-1.80) 0.30 (0.10-0.80)
0.03
0.18 0.37 0.009
1 (ref)
0.83 (0.34-2.05) 0.45 (0.14-1.45) 0.33 (0.14-0.81)
0.01 -
0.69 0.18 0.02
Reduction ≥70% in tumor size on PPMRI results 0.46 (0.27-0.78) 0.004 0.42 (0.23-0.77) 0.005
Incomplete response on PPMRI 1.20 (0.70-1.90) 0.55 - -
Table 2. Identification of prognostic factors of recurrence. HR: Hazard Ratio; HRa: Adjusted Hazard; BMI: Body Mass Index; CRT: chemoradiation therapy; PPMRI: posttreatment pelvic MRI. * Compared to IB2 stage (reference) ** Compared to other histology type † Compared to N- patients (reference) ‡ Compared to patients treated with exclusive CRT (reference)
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Figure 1. Recurrence-free (A) and overall (B) survivals based on posttreatment PMRI results
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Predictive factors for death
The 5-year OS for patients with an incomplete response at PPMRI was 78.4% vs. 84.6% for
patients with a complete response (p=0.047) (Figure 1B). An incomplete response at PPMRI
was not identified as a significant risk factor of death (Table 3). The best prediction in
patients’ OS was found for the same threshold of 70% reduction or more in tumor’s size with
a 50% sensitivity and 77.9% specificity. Thus, a reduction ≥70% in tumor’s size was the only
factor identified to significantly prevent the risk of death (HRa: 0.18; 95%CI: 0.06-0.50;
p=0.001) (Table 3).
HR (95 % CI) p HRa (95 % CI) p
Age (for each extra year) 0.99 (0.96-1.03) 0.63 - -
BMI (for 1 kg/m² extra) 0.98 (0.91-1.06) 0.60 - - Parity (for 1 extra birth) 1.13 (0.99-1.29) 0.07 - - Menopaused 0.70 (0.30-1.50) 0.31 - -
FIGO stage * IB2 IIA IIB
1 (ref.)
0.40 (0.10-1.70) 0.50 (0.20-1.20)
0.24 -
0.19 0.14
1 (ref.)
0.30 (0.03-2.58) 0.41 (0.15-1.14)
0.19 -
0.27 0.09
Squamous carcinoma ** 2.30 (0.50-9.60) 0.27 6.37 (0.80-50.8) 0.08 Tumor size (for each extra mm) 1.03 (1.00-1.06) 0.07 1.03 (0.99-1.07) 0.11 Nodal status †
N- Nx N+
1 (ref.)
1.50 (0.60-4.20) 2.70 (1.10-7.10)
0.11 -
0.42 0.04
1 (ref.)
1.98 (0.61-6.39) 1.60 (0.52-4.92)
0.50 -
0.25 0.41
Treatment modality ‡ CRT CRT + VBT CRT + Completion hysterectomy CRT + VBT + Completion hysterectomy
1 (ref.)
0.30 (0.10-1.10) 0.90 (0.20-3.90) 0.20 (0.10-0.90)
0.03 -
0.08 0.92 0.03
1 (ref.)
0.47 (0.11-2.08) 0.46 (0.09-2.41) 0.27 (0.06-1.16)
0.36 -
0.32 0.36 0.08
Reduction ≥70% in tumor size on PPMRI results
0.27 (0.12-0.62) 0.002 0.18 (0.06-0.50) 0.001
Incomplete response on PPMRI 2.30 (1.00-5.40) 0.05 - - Table 3. Identification of prognostic factors of death. HR: Hazard Ratio; HRa: Adjusted Hazard; BMI: Body Mass Index; CRT: chemoradiation therapy; PPMRI: posttreatment pelvic MRI. * Compared to IB2 stage (reference) ** Compared to other histology types † Compared to N- patients (reference) ‡ Compared to patients treated with exclusive CRT (reference)
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Diagnostic performances of PPMRI in predicting cervical residual disease
When only considering the 117 patients who had undergone completion surgery, MRI
sensitivity and specificity in predicting histologic cervical residual disease was 75% (95% CI:
63-86) and 51% (95%CI: 38-63), respectively (Table 4). MRI diagnostic performances were
not impacted by histology, with comparable results in patients with squamous cervical
cancers and others. Only the size of the histologic cervical residue was found to impact the
diagnostic performances of PPMRI. Diagnostic performances were better when the size of
histologic residual disease was ≥10 mm, with 89.7 % sensitivity vs. 50.0% for smaller
residues (p=0.005).
Cervical residual disease on hysterectomy specimen
No Yes Total
Incomplete response on
posttreatment pelvic MRI
No 31 (50.8) 14 (25.5) 45 (38.8)
Yes 30 (49.2) 41 (74.5) 71 (61.2)
Total 61 55 116
Table 4. Diagnostic performances of posttreatment pelvic MRI in predicting documented histologic cervical residual disease in completion hysterectomy specimens after CRT. All values are expressed as n (%)
Ability of PPMRI to select patients who could benefit from completion surgery
While survival of patients found to have complete response at PPMRI was not impacted by
the practice of completion surgery, significant increase in RFS and OS was observed in
patients who had undergone completion surgery following the diagnosis of incomplete
response at posttreatment PMRI. Thus, among these patients, 5-year RFS was of 65.3% when
completion surgery was performed vs 38.7% when not performed (p<0.001); 5-years OS was
82.9% vs 63% (p=0.038), respectively (Figure 2).
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Figure 2. Recurrence-free (A) and overall (B) survivals in cases of incomplete response on
posttreatment PMRI depending on whether completion surgery was performed or not.
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DISCUSSION
This study shows systematic PPMRI to be predictive of the prognosis of patients treated with
CRT for locally advanced cervical cancer. Best prediction was achieved for patients showing
a 70% or more reduction in the dimensions of the lesion. Additionally, PPMRI demonstrated
genuine abilities in predicting cervical histologic residual disease, especially when histologic
residual disease was10 mm or more.
Our results suggest PPMRI to be a suitable tool for triaging patients that could benefit from
completion surgery. Thus, although patients with PPMRI complete response did not show any
benefit in undergoing completion surgery, it significantly improved both RFS and OS in
patients with incomplete response. The debate about whether or not completion surgery
should be performed following CRT has been ongoing for decades. At this stage, available
published data reported no obvious benefit of completion surgery but genuine morbidity
[18,20,20,23]. Our results are consistent with this statement as the sole practice of completion
surgery did not demonstrate any improvement in patients risk of recurrence, nor death (tables
2 and 3). Previous data suggest that completion surgery could be beneficial in selected
patients with documented post RCT residual cervical disease and of no therapeutic impact in
patients with complete response following CRT [19,27]. Such approach is consistent with our
findings. Although our results suggest completion surgery does not improve outcomes of
patients that achieved complete response at PPMRI, this option seems genuinely worthwhile
in selected cases showing incomplete response and should therefore be considered.
With a 70% threshold in the reduction of the initial dimension of the lesion identified as the
best predictor for outcome, our findings raise concerns regarding the possibility of time-
related ongoing effects of CRT. Indeed, as PPMRI were performed within a 3 month delay
following the completion of CRT, it is possible that patients had achieved complete histologic
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response after PPMRI had been performed. This could at least partially explain why, among
71 patients found with incomplete response on PPMRI, 30 (42.3%) finally showed no
histologic residue on hysterectomy specimen (Table 4). This hypothesis is supported by
previous published data showing that early MRI evaluation of cervical cancer’s response to
CRT is less reliable if performed too early, with increased risk of false positive results when
performed before a 3 months delay [13,17]. The delay in which imaging exams should be
performed following CRT remains widely discussed. To date, there is still no consensus about
the optimal time delay when PPMRI should be performed following RCT and practice was
shown to vary from 3 weeks to 6 months after completion of CRT across Europe [11]. As
morbidity of completion surgery directly depends on the delay following CRT and increases
with time, it is however crucial that imaging should be performed early enough to enable
surgery to be considered and organized. Unfortunately, the exact date when PPRMI had been
performed were not properly documented in a majority of patients’ medical charts, therefore
not allowing for a precise estimation of the impact of delay following CRT on the prediction
of histologic residual disease. We believe this point to be of major importance when
interpreting our results and considering exporting those to clinical routine practice as our
results cannot be extrapolated to PPMRI performed after the delay of 3 months reported here.
Additionally to the possible time related delay in CRT effect, our results suggest performance
of PPMRI to directly depend on the dimensions of cervical residual disease. Thus, only
histologic residue of 10 mm or more are likely to be properly identified by PPMRI. This
finding provides additional information on the possible reasons and risks of false negative
results of PPMRI. Due to the retrospective nature of our analysis, we were not able to provide
reliable information regarding MRI types and characteristics, precise MRI sequences used and
imaging evaluation. We acknowledge this point to represent a major limitation that should be
carefully considered when interpreting our results. It is thus unfortunate that we were not able
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to identify the impact of diffusion-weighted PPMRI on its performance and to assess values
of changes in cervical tumour’s apparent diffusion coefficient as this data was not
systematically recorded. Because it showed high value for the evaluation of tumour viability
and prediction of treatment efficacy, this technique is currently routinely used in all our
participating centres for PPMRI evaluation [28–32]. With our retrospective analysis running
for a 20 year period, only most recent PPMRI examinations from our cohort were likely to
have used diffusion-weighted technique. Although we were not able to specifically assess the
benefit of this technique, we did not observe any significant change of PPMRI prognosis
value over time when assessing the impact of time on patients’ outcome.
CONCLUSIONS
Systematic PPMRI is predictive of the prognosis of patients treated with CRT for locally
advanced cervical cancer. Best prediction in patients’ prognosis was achieved when a
reduction of 70% or more in the dimensions of the lesion was observed. Finally, PPMRI
demonstrated high sensitivity in predicting cervical histologic residual disease, with optimal
prediction achieved for histologic residual disease of at least 10 mm. It therefore could help
for the identification of patients with histologic residual disease and therefore for the triage of
patients that could benefit from completion surgery. Thus, in patients with IB2-IIB cervical
cancer, although the identification of complete response at PPRMI performed within 3
months after CRT does not support the practice of completion surgery, it should be
considered in patients with incomplete response.
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Conflict of Interest’ statement: All authors have no conflict of interest to declare.
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Conflict of Interest’ statement: All authors have no conflict of interest to declare.
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